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Biomedical subjects

M Schulzer

Publications and source records attributed to M Schulzer.

At least 19 recordsLinked to original sources

The natural history of neurological manganism over 18 years.

We investigated the clinical features and progression of four patients with chronic manganese intoxication, 18 years after cessation of exposure. Because the results were to be compared with previous observations, we employed the same scoring system. The clinical manifestations were foot dystonia, wide based gait, rigidity, and difficulty in walking backwards. Resting tremor was rarely seen, but tongue tremor was found in 2 patients. The asymmetry initially present in 2 patients persisted 18 years later. Measurements had previously revealed rapid progression in the initial 10 years. We found a plateau over the following decade.

Disease Progression↗

Reduction in IV t-PA door to needle times using an Acute Stroke Triage Pathway.

OBJECTIVE: To determine the effectiveness of an Acute Stroke Triage Pathway in reducing door to needle times in acute stroke treatment with IV t-PA. BACKGROUND: A previous study at our tertiary referral centre, examining IV t-PA door to needle times, was completed in 2000. The median door to needle time was beyond the recommended National Institute for Neurological Disorders and Stroke (NINDS) standard of 60 minutes. In November 2001, an Acute Stroke Triage Pathway was introduced in the emergency room (ER) to address this issue. The goal of this pathway was to rapidly identify patients eligible for treatment for IV t-PA, so that CT scans and lab studies could be arranged immediately upon ER arrival. Our hypothesis was that the Triage Pathway would shorten door to CT and door to needle times. DESIGN/METHODS: Using retrospective data, pre (n=87) and post (n=47) triage pathway times were compared. The door to CT time was reduced by 11 minutes (p=0.015) and door to needle time was reduced by 18 minutes (p=0.0036) in a subgroup of patients that presented directly to our hospital. CONCLUSIONS: These results indicate that the Acute Stroke Triage Pathway is effective in reducing Door to CT and Door to Needle Times in patients presenting directly to our ER. However, a majority of treatment times were still beyond NINDS recommendations. Stroke Centers require periodic review of their efficiency to ensure that target times are being obtained and may benefit from the use of an Acute Stroke Triage Pathway.

Acute Disease↗

A population-based study of risk factors for drug-resistant TB in British Columbia.

SETTING: Provincial tuberculosis (TB) services, British Columbia, Canada. OBJECTIVE: To investigate risk factors associated with resistance to anti-tuberculosis drugs in British Columbia and to determine if there are differences in risk factor characteristics among different resistance categories. DESIGN: Using population-based data from provincial TB services, all patients with positive culture for Mycobacterium tuberculosis from 1990 to 2001 were identified and included in the study. Logistic regression analyses were performed to assess risk factors for drug resistance. RESULTS: Among 3041 eligible TB cases, 295 (10%) were found to be drug-resistant. Significant risk factors for resistance were younger age, foreign birth, ethnicity, reactivated TB and place of initial diagnosis. Foreign-born subjects (OR 3.18, 95%CI 2.26-4.49) were three times more likely to present with resistance than Canadian-born subjects. Among ethnic groups, Chinese (OR 2.32, 95%CI 1.51-3.57), South-East Asian (OR 2.92, 95%CI 1.88-4.52) and Other Asian subjects (OR 4.40, 95%CI 2.77-7.01) were 2-4 times more likely to present with resistance than Caucasians. Reactivated cases (OR 2.69, 95%CI 1.91-3.77) were three times as likely to have resistance as new cases. CONCLUSION: These results document and quantify the risk of drug-resistant disease in a large population-based cohort, and highlight patient groups who should be identified as at risk for drug-resistant disease in the industrialised world.

Adolescent↗

Impact of country of origin on drug-resistant tuberculosis among foreign-born persons in British Columbia.

SETTING: Provincial tuberculosis (TB) services, British Columbia, Canada. OBJECTIVES: To estimate the risk of drug resistance among foreign-born TB patients and to identify risk factors associated with drug resistance. DESIGN: Using the provincial TB database, we examined all culture-positive foreign-born TB patients for the years 1990-2001. The risk of having a drug-resistant isolate was estimated according to country and region of origin. RESULTS: Of 1940 foreign-born patients identified, 247 (12.7%, 95%CI 11.3-14.3) cases had isolates resistant to at least one of the first-line drugs, with 160 (8.3%) isolates showing monoresistance, 24 (1.2%) multidrug resistance (resistance to at least isoniazid and rifampin) and 63 (3.3%) polyresistance (resistance to two or more drugs, excluding MDR). Country-specific analysis showed that immigrants from Vietnam (adjusted OR 2.12, 95%CI 1.37-3.27) and the Philippines (adjusted OR 1.71, 95%CI 1.10-2.66) had a significantly higher risk of resistance than other immigrants. In addition, the risk was the highest for younger TB patients and patients with reactivated disease (adjusted OR 2.12, 95%CI 1.09-4.09). CONCLUSION: The risk of drug resistance was the highest among foreign-born patients from Vietnam and the Philippines. These findings should assist clinicians in prescribing and tailoring anti-tuberculosis regimens for immigrants more appropriately.

Adolescent↗

Diagnostic accuracy of self collected vaginal specimens for human papillomavirus compared to clinician collected human papillomavirus specimens: a meta-analysis.

BACKGROUND/OBJECTIVES: Providing summary recommendations regarding self collection of vaginal specimens for human papillomavirus (HPV) testing is difficult owing to the wide range of published estimates for the diagnostic accuracy of this approach. To determine summary estimates from analyses of reported findings of the sensitivity, specificity and summary receiver operating characteristic curves (SROC) for self collected vaginal specimens for HPV testing compared to the reference standard, clinician collected HPV specimens. METHODS: Standard search criteria for a diagnostic systematic review were employed. Eligible studies were combined using a random effects model and summary ROC curves were derived for overall and for specific subgroups. RESULTS: Summary measures were determined from 12 studies. Six studies where patients used Dacron or cotton swabs or cytobrushes to obtain samples were pooled and had an overall sensitivity of 0.74 (95% CI 0.61 to 0.84) and specificity of 0.88 (95% CI 0.83 to 0.92), with diagnostic odds ratio of 22.3 and an area under the curve of 0.91. Self specimens using Dacron or cotton swabs or cytobrushes collected by women enrolled at referral clinics had an overall sensitivity of 0.81 (95% CI 0.65 to 0.91) and specificity of 0.90 (95% CI 0.80 to 0.95). Sensitivity and specificity of tampons ranged from 0.67-0.94 and 0.80-0.85 respectively. CONCLUSIONS: Our findings indicate that the combined sensitivity for HPV-DNA is more than 70% when patients use Dacron swabs, cotton swabs, or cytobrushes to obtain their own vaginal specimens for HPV-DNA evaluation. Self collected HPV-DNA swabs may be an appropriate alternative for low resource settings or in patients reluctant to undergo pelvic examinations.

Area Under Curve↗

Nocturnal sleep disturbances and daytime dysfunction in patients with Parkinson's disease and in their caregivers.

BACKGROUND: The role of aging, disease, medications, and mood disturbances in sleep disturbances (SD) in patients with Parkinson's disease (PD) is poorly understood, and the impact of SD on the quality of life of their caregivers (CG) largely undocumented. OBJECTIVES: To evaluate the pattern and determinants of disturbed sleep in PD patients complaining of SD, and in their primary CG. METHODS: A prospective evaluation of 40 non-demented patients with PD complaining of SD and 23 of their primary CG (all were spouses) was conducted using Pittsburgh Sleep Quality Index, Zung's self-rating depression and anxiety scales, Parkinson's Impact Scale (PIMS) (only for PD), and an additional sleep questionnaire. RESULTS: Eighty-four percent of patients were 'poor sleepers' with global sleep scores (GLSc) > 5. Other abnormalities were: excessive daytime sleepiness-57.5%, excessive daytime fatigue-72.5%, depression-51.5%, anxiety-63.1%, and abnormal PIMS score-83.8%. There was no correlation between the degree of sleep dysfunction and the age, severity, duration of PD or its treatment. Several component sleep scores correlated with anxiety scores, PIMS score with depression, and, subjects with GLSc > or = 10 had higher mean anxiety index. Daytime dysfunction (97.5%) was mainly associated with reduced enthusiasm, rather than excessive sleepiness. Among CG, 40% had a GLSc > 5, 21% had depression, and 10.5% had anxiety. Their depression, anxiety and sleep scores correlated with those of their spouses. CONCLUSIONS: PD patients with significant SD may represent a subset of patients with early, progressive degeneration of sleep centres, rather than an enhanced aging process. They are more susceptible mood disturbances, which correlate with the severity of sleep dysfunction. Sleep and mood disturbances also adversely affect the quality of life of spousal caregivers.

Adult↗

Familial and sporadic Parkinson's disease usually display the same clinical features.

We examined the clinical features of familial (n = 26) and sporadic (n = 52) Parkinson's disease (PD) in patients presenting over the age of 40 years. Familial PD cases were tested for alpha-synuclein or parkin mutations as appropriate. No mutations were found in any of the families investigated. We found no between-group differences in the age at onset of PD, the pattern or severity of parkinsonian features, the dose of antiparkinsonian medications or treatment related complications. Cases of familial and sporadic PD in our cohort of patients display similar clinical features. This may suggest similar etiologies for both familial and sporadic PD.

Antiparkinson Agents↗

The prevalence of Parkinson's disease in British Columbia, Canada, estimated by using drug tracer methodology.

OBJECTIVE: To estimate the prevalence of Parkinson's disease (PD) in British Columbia utilizing the prescription database of the College of Pharmacists. METHODS: Patients receiving anti-parkinsonian drug (anti-PD) prescriptions between 1996 and 1998 were stratified by year, age, gender, drug use category, and geographic location. The numbers of patients on levodopa alone, or levodopa and/or other anti-PD drugs were adjusted using published data which gave estimates of the proportion of undiagnosed patients with PD, the proportion of those treated for parkinsonism with definite PD, the proportion of patients with PD not being treated with anti-PD medications, and the proportion of patients treated with anti-PD medications who have PD. Use of the anti-PD drug bromocriptine for other purposes in women under 50 years of age was also considered. RESULTS: The estimated prevalences of PD based on all anti-PD medications used were 109, 121, and 125 per 100,000 population in 1996, 1997, and 1998, respectively. Estimated prevalences of PD based on levodopa use were 126, 134, and 144, respectively. The prevalence in both prescription groups increased with age. The male to female ratio of prevalence ranged from 1.16 to 1.21. CONCLUSIONS: Using a large, accurate database, it is possible to estimate the prevalence of PD in a large population, though the assumptions built into the estimate remain to be validated in the subject population.

Adult↗

A meta-analysis of the effect of Bacille Calmette Guérin vaccination on tuberculin skin test measurements.

BACKGROUND: The accurate diagnosis of latent tuberculosis infection (LTBI) is an important component of any tuberculosis control programme and depends largely on tuberculin skin testing. The appropriate interpretation of skin test results requires knowledge of the possible confounding factors such as previous BCG vaccination. Uncertainty about the effect of BCG vaccination on tuberculin skin testing and the strength with which recommendations are made to individual patients regarding treatment of LTBI have identified a need to analyse the available data on the effect of BCG on skin testing. A meta-analysis of the evidence for the effect of BCG vaccination on tuberculin skin testing in subjects without active tuberculosis was therefore performed. METHODS: Medline was searched for English language articles published from 1966 to 1999 using the key words "BCG vaccine", "tuberculin test/PPD", and "skin testing". Bibliographies of relevant articles were reviewed for additional studies that may have been missed in the Medline search. Articles were considered for inclusion in the meta-analysis if they had recorded tuberculin skin test results in subjects who had received BCG vaccination more than 5 years previously and had a concurrent control group. Only prospective studies were considered. The geographical location, number of participants, type of BCG vaccine used, type of tuberculin skin test performed, and the results of the tuberculin skin test were extracted. RESULTS: The abstracts and titles of 980 articles were identified, 370 full text articles were reviewed, and 26 articles were included in the final analysis. Patients who had received BCG vaccination were more likely to have a positive skin test (5 TU PPD: relative risk (RR) 2.12 (95% confidence interval (CI)1.50 to 3.00); 2 TU RT23: 2.65 [corrected] (95% CI 1.83 to 3.85). The effect of BCG vaccination on PPD skin test results was less after 15 years. Positive skin tests with indurations of >15 mm are more likely to be the result of tuberculous infection than of BCG vaccination. CONCLUSIONS: In subjects without active tuberculosis, immunisation with BCG significantly increases the likelihood of a positive tuberculin skin test. The interpretation of the skin test therefore needs to be made in the individual clinical context and with evaluation of other risk factors for infection. The size of the induration should also be considered when making recommendations for treatment of latent infection.

BCG Vaccine↗

Expectation and dopamine release: mechanism of the placebo effect in Parkinson's disease.

The power of placebos has long been recognized for improving numerous medical conditions such as Parkinson's disease (PD). Little is known, however, about the mechanism underlying the placebo effect. Using the ability of endogenous dopamine to compete for [11C]raclopride binding as measured by positron emission tomography, we provide in vivo evidence for substantial release of endogenous dopamine in the striatum of PD patients in response to placebo. Our findings indicate that the placebo effect in PD is powerful and is mediated through activation of the damaged nigrostriatal dopamine system.

Aged↗

Biochemical variations in the synaptic level of dopamine precede motor fluctuations in Parkinson's disease: PET evidence of increased dopamine turnover.

Motor fluctuations are a major disabling complication in the treatment of Parkinson's disease. To investigate whether such oscillations in mobility can be attributed to changes in the synaptic levels of dopamine, we studied prospectively patients in the early stages of Parkinson's disease with a follow-up after at least 3 years of levodopa treatment. At baseline, 3 positron emission tomography (PET) scans using [11C]raclopride before and after (1 hour and 4 hours) orally administered levodopa were performed on the same day for each patient. Patients who developed "wearing-off" fluctuations during the follow-up period had a different pattern of levodopa-induced changes in [11C]raclopride binding potential (BP) from that observed in patients who were still stable by the end of the follow-up. Thus, 1 hour post-levodopa the estimated increase in the synaptic level of dopamine was 3 times higher in fluctuators than in stable responders. By contrast, only stable responders maintained increased levels of synaptic dopamine in the PET scan performed after 4 hours. These results indicate that fluctuations in the synaptic concentration of dopamine precede clinically apparent "wearing-off" phenomena. The rapid increase in synaptic levels of dopamine observed in fluctuators suggests that increased dopamine turnover might play a relevant role in levodopa-related motor complications.

Brain↗

Risk factors for progression of visual field abnormalities in normal-tension glaucoma.

PURPOSE: To uncover risk factors for the highly variable individual rates of progression in cases of untreated normal-tension glaucoma. METHODS: Visual field data were assembled from 160 subjects (160 eyes) enrolled in the collaborative normal-tension glaucoma study during intervals in which the eye under study was not receiving intraocular pressure-lowering treatment during prerandomization and postrandomization intervals. Analyses included multivariate analysis of time-dependent Cox proportional hazard, Kaplan-Meier analysis of "survival" without an increment of visual field worsening, and comparison of slopes of change in mean deviation global index over time. RESULTS: Most migraine occurred in women, but analysis demonstrated that gender and presence of migraine contribute separately to the overall risk. The risk ratio for migraine, adjusted for the other variables was 2.58 (P =.0058), for disk hemorrhage was 2.72 (P =.0036), and for female gender 1.85 (P =.0622). The average fall in the mean deviation index was faster in nonmigrainous women than in nonmigrainous men (P =.05). Suggesting genetic influence, Asians had a slower rate of progression (P =.005), and the few black patients enrolled had a tendency for faster progression. However, self-declared history of family with glaucoma or treated for glaucoma did not affect the rate of progression. Neither age nor the untreated level of intraocular pressure affected the rate of untreated disease progression, despite their known influence on prevalence. CONCLUSIONS: Whereas risk factors for prevalence help select populations within which to screen for glaucoma, the factors that affect the rate of progression help decide the expected prognosis of the individual's untreated disease and thereby the frequency of follow-up and aggressiveness of the therapy to be undertaken.

Aged↗

Natural history of normal-tension glaucoma.

OBJECTIVE: A recently reported randomized study described the role of intraocular pressure (IOP) in normal-tension glaucoma (NTG) pathogenesis and the effect of therapeutic lowering of IOP. This is a report of an analysis of the natural course of NTG during the time eyes were not receiving therapy, either in the time interval awaiting randomization or after being randomly assigned not to receive treatment to lower the IOP. DESIGN: Analysis of prospectively collected data on the long-term course of a cohort of untreated subjects with normal-tension glaucoma, a subset of subjects enrolled in a randomized controlled clinical trial. RANDOMIZATION AND SUBJECT SELECTION: If the field defect in the study eye threatened the point of fixation, the subject was randomly assigned to start on treatment immediately or to be observed without treatment until progression was documented. Otherwise, an eye was randomly assigned only when and if, subsequent to enrollment, it showed visual field progression, progression of optic disc cupping, or a new disc hemorrhage. PARTICIPANTS: Data were collected for this report on 160 subjects observed without treatment among a total enrollment of 260. They consist of 49 subjects who were randomly assigned on enrollment not to receive therapy, 24 followed without treatment for a time until later being randomly assigned to treatment, 31 similarly followed without treatment and who were later randomly assigned to be followed for an additional time without treatment, and 56 who enrolled but were never randomly assigned. MAIN OUTCOME MEASURES: Visual field data were used in this report only from the interval during which the eye had not been assigned to receive therapy and were analyzed by two measures of progression: the "survival" time to meeting a criterion of confirmed localized progression and the rate of change in the mean deviation (MD) index over time. RESULTS: The four subgroups just described were similar at baseline, except that the average MD index was slightly better for the 56 eyes that never progressed during the period of follow-up. By Kaplan-Meier analysis of all untreated subjects combined, approximately one third showed localized progression within 3 years and about half within 5 to 7 years. Of subjects followed for 3 years or more, 62 of 109 did not show a statistically significant negative slope of MD regressed over time, whereas the others showed a statistically significant MD decline, mainly between -0.2 and -2 db per year. CONCLUSIONS: Some cases of NTG progress more rapidly than others. Although approximately half of cases showed a confirmed localized visual field deterioration by 7 years, the change is typically small and slow, often insufficient to measurably affect the MD index.

Aged↗

Alternating two finger tapping with contralateral activation is an objective measure of clinical severity in Parkinson's disease and correlates with PET

We explored an objective method of measuring clinical severity of Parkinson's disease. Eighty-six patients with PD and 136 healthy subjects were studied. We serially carried out four types of finger tapping (FT) using a computerized drum machine: (i) repetitive one-finger tapping with an index-finger (F1K1); (ii) one-finger tapping on two keys separated by 20cm (F1K2); (iii) alternate tapping with index and middle fingers on two adjacent keys (F2K2); and (iv) F2K2 with contralateral activation (aF2K2). Analyses on FT included: (i) age and gender effects in healthy volunteers and Parkinson's disease; (ii) comparison between Parkinson patients and controls of similar age distribution; (iii) correlation with the Purdue Pegboard and Modified Columbia Scale in Disease; and (iv) in a subset of patients in whom PET scans were performed (n=30), correlation with 18F-DOPA uptake constant (Ki). In healthy subjects, there was a negative age effect on FT scores and a gender effect, with males scoring higher than females. All FT scores were significantly lower in the Parkinson patients, correlated with Purdue Peg Board, and inversely with the duration of illness, and with the Modified Columbia Scale. The 18F-DOPA Ki correlated significantly with aF2K2 (p=0.024), less so with PPB (p=0.038), but not with the Modified Columbia Scale. We conclude that alternating two-finger tapping with contralateral hand activation is a simple, objective test for measuring the severity of Parkinson's disease.

Journal Article↗

Daytime somnolence in patients with Parkinson's disease.

We studied daytime sleepiness in 160 patients with Parkinson's disease and 40 normal subjects. We compared the prevalence of daytime sleepiness in patients who were taking levodopa alone, levodopa with bromocriptine, levodopa with ropinirole, and levodopa with pramipexole. We found that (1) all these anti-Parkinson drugs can cause daytime sleepiness; (2) 'dozing off' correlated highly with 'falling asleep without warning'; (3) after statistical adjustment for confounding variables there was no significant difference among the risks for any of these anti-Parkinson drugs causing daytime somnolence.

Journal Article↗

Survival analysis for success of Molteno tube implants.

AIM: To apply survival analysis in assessing the long term outcome of Molteno tube implantation and to identify risk factors for failure. METHODS: A retrospective, 10 year, consecutive case series study of 119 eyes that underwent implantation of a Molteno tube. The main outcome measures considered were intraocular pressure (IOP), visual acuity, and complications. RESULTS: A 30% or greater reduction in IOP was achieved in 68.9% of cases. However, the overall, "complete success" rate (IOP <22 mm Hg with no medications) after a mean (SD) follow up period of 43 (33) months (range 6-120) was only 33.6% despite a fall in mean (SD) IOP from 38.2 (8.2) mm Hg to 20.1 (11.0) mm Hg. The "qualified success" rate (IOP <22 mm Hg with or without medications) was 60.5%. Failure was most common in the first postoperative year but could occur after several years, the survival curve having an exponential shape. The only statistically significant risk factor for failure identified was pseudophakia, although eyes with neovascular glaucoma tended to fare poorly. Postoperative IOP tended to be lower after double plate than after single plate implantation. There was no significant difference in outcome based on age, sex, race, previous penetrating keratoplasty, or previous conjunctival surgery. CONCLUSIONS: In eyes at high risk of trabeculectomy failure, implantation of an aqueous shunt device should be considered. Pseudophakia should be considered an additional risk factor for failure. Early failure appeared relatively more common but long term follow up of all cases is recommended to ensure adequate management of late failures.

Adult↗

Microelectrode recording for pallidotomy: mandatory, beneficial or dangerous?

There is an active debate regarding whether pallidotomy should be performed with microelectrode recording or macroelectrode stimulation. A meta-analysis was performed on the published reports (1992-2000) of unilateral pallidotomy for Parkinson's disease to determine if the outcome or complications of this procedure significantly differed between these two techniques. Papers were excluded if they followed a cohort of less than ten patients, had follow-up less than three months, or included previously reported patients. There were no significant differences between the two techniques in improvement of dyskinesia (p = 0.66) or UPDRS motor score (p = 0.62). Microelectrode recording had a significantly higher (p = 0.012) intracerebral hemorrhage rate (1.3 +/- 0.4%) compared to macroelectrode stimulation (0.2 +/- 0.2%).

Brain Damage, Chronic↗